crossing96/oncoscreening huggingface dataset:
Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival.	BACKGROUND: To retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution. METHODS: Between July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment. RESULTS: The numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity. CONCLUSIONS: Our result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder cancer.	bladder
Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.	Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.	bladder
Recent advances in imaging cancer of the kidney and urinary tract.	Modern radiologic imaging is an aid to treatment planning for localized renal cancer, enabling characterization of mass lesions. For patients who present with advanced renal cancer, new imaging techniques enable a functional assessment of treatment response not possible using anatomic measurements alone. Multidetector CT urography permits simultaneous assessment of the kidneys and urinary tract for patients with unexplained hematuria. Both CT and MRI play a significant role in staging and follow up of patients treated for urothelial cancer. Newer imaging methods such as diffusion-weighted MRI have shown promising results for improving accuracy of staging and follow up of urothelial cancer.	bladder
Complication of treatment of carcinoma in situ of the bladder with photodynamic targeted cystodiathermy.	We report two cases of bladder contracture following photodynamic or 'blue light' detection and cystodiathermy for bladder carcinoma in situ. These patients were unsuitable for treatment with immunotherapy/chemotherapy or had disease recurrence following such treatment. Radical cystectomy was not a treatment option in either patient. Each underwent serial photodynamic cystodiathermy over a three-year period. Neither patient developed muscle invasive disease. However, treatment resulted in contracture of the bladder and incontinence of urine. Patients need to be fully aware of this potential complication in order to make informed choices about their care.	bladder
Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis.	BACKGROUND: Inflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer. METHODS: Sixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan-Meier curves and compared by the log-rank test. RESULTS: In our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27-3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31-19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63-4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60-8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance. CONCLUSIONS: The LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.	bladder
Recombinant bacillus Calmette-Guérin in urothelial bladder cancer immunotherapy: current strategies.	Bacillus Calmette-Guérin (BCG) has been used in the intravesical treatment of urothelial bladder cancer (UBC) for three decades. Despite its efficacy, intravesical BCG therapy is associated with some limitations such as side effects and BCG failure, which have inspired multiple ways to improve it. Recent advances have focused on recombinant BCG (rBCG) which provides a novel tactic for modification of BCG. To date, a number of rBCG strains have been developed and demonstrated to encourage efficacy and safety in preclinical and clinical studies. This review summarizes current rBCG strategies, concerns and future directions in UBC immunotherapy with an intention to encourage further research and eventually to inform clinical decisions.	bladder
Bladder cancers arise from distinct urothelial sub-populations.	Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences.	bladder
Y pouch neobladder-a simplified method of intracorporeal neobladder after robotic cystectomy.	In recent years, robot-assisted radical cystectomy (RARC) has shown similar oncologic outcomes compared with the gold standard open radical cystectomy with the added benefit of less blood loss and shorter hospital stay. Robot-assisted cystectomy with intracorporeal ileal neobladder is a complex surgical procedure and is usually performed in centers with experienced surgeons. We propose robot-assisted cystectomy with intracorporeal neobladder using the Y pouch previously described in open radical cystectomy. We think that the Y pouch is easier to perform than conventional spherical pouches without compromising functional outcomes. It may therefore be a good alternative for patients undergoing RARC with intracorporeal diversion.	bladder
[Should we propose a systematic second transurethral resection of the bladder for all high-risk non-muscle invasive bladder cancers?].	OBJECTIVE: Quantify the rate of residual bladder tumor following systematic second look resection of pTa high-grade versus pT1 high-grade patients. MATERIAL AND METHODS: From January 2010 to July 2013, 53 patients with a non-muscle-invasive bladder cancer with high-risk of recurrence and progression underwent a second systematic resection in accordance with the current guidelines of the French Association of Urology (AFU). RESULTS: Among the 53 patients with a high-risk non-muscle-invasive bladder cancer, histological examination of the initial resection identified: 17 pTa high-grade (32.1%) and 36 pT1 high-grade (67.9%). There was a significant difference between the 2 groups of patients (Ta high-grade versus T1 high-grade) concerning the rate of residual tumor on second look resection (11.8% versus 66.7%, P=0.0002). The predictive factors of residual tumor after second resection were the pT1 stage (P=0.0002), tumor multifocality (P=0.02) and presence of associated Cis (P=0.0005). CONCLUSION: The high rate of residual tumor in our series confirmed the importance of a systematic second look resection for high-risk non-muscle-invasive bladder cancers. However, for the pTa tumors without associated Cis, the interest of this second look seemed of less concern. LEVEL OF EVIDENCE: 5.	bladder
Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.	Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran-Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥ 2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥ 2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III-IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not expressed. Ten normal bladder specimens demonstrated ≤ 1+ staining for IL-4Rα and IL-13Rα1 and no staining for IL-2RγC. These results demonstrate that IL-4Rα is overexpressed in human bladder cancer, which correlates with advanced grade and stage of the disease. Thus, IL-4Rα may be a bladder tumor-associated protein and a prognostic biomarker.	bladder
Chemical modification of a tetrapyrrole-type photosensitizer: tuning application and photochemical action beyond the singlet oxygen channel.	Reactive oxygen species (ROS) formed by light activated photosensitizers (PSs) are the hallmark of photodynamic therapy (PDT). It is generally accepted that commonly used PSs generate singlet oxygen ((1)O2) as the cell-toxic species via type II photosensitization. We explored here the consequences of chemical modification and the influence of the net charge of a cationic tetrahydroporphyrin derivative (THPTS) relative to the basic molecular structure on the red-shift of absorption, solubility, mechanistic features, and photochemical as well as cell-toxic activity. In order to shed light into the interplay between chemical modification driven intra- and intermolecular photochemistry, intermolecular interaction, and function, a number of different spectroscopic techniques were employed and our experimental studies were accompanied by quantum chemical calculations. Here we show that for THPTS neither (1)O2 nor other toxic ROS (superoxide and hydroxyl radicals) are produced directly in significant quantities in aqueous solution (although the formation of singlet oxygen is energetically feasible and as such observed in acetonitrile). Nevertheless, the chemically modified tetrapyrrole photosensitizer displays efficient cell toxicity after photoexcitation. The distribution and action of THPTS in rat bladder caricinoma AY27 cells measured with fluorescence lifetime imaging microscopy shows accumulation of the THPTS in lysosomes and efficient cell death after irradiation. We found evidence that THPTS in water works mainly via the type I mechanism involving the reduction rather than oxidation of the excited triplet state THPTS(T1) via efficient electron donors in the biosystem environment and subsequent electron transfer to produce ROS indirectly. These intriguing structure-activity relationships may indeed open new strategies and avenues in developing PSs and PDT in general.	bladder
Complex mucinous cystadenoma of undetermined malignant potential of the urachus: a rare case with review of the literature.	Urachal carcinoma is an uncommon neoplasm. Benign urachal tumours are extremely rare. All urachal mucinous tumours, regardless of tumour type, have the potential to behave in an aggressive clinical manner that includes the development of pseudomyxoma peritonei. We report a 58-year-old man who presented with lower abdominal pain. Ultrasound and CT imaging defined a large lobulated cystic mass superior to the urinary bladder. At laparotomy, the multiloculated cystic mass, 10 x 8 x 6 cm, could be completely separated from the bladder and was excised. It was smooth-walled and filled with thick mucinous fluid. Histology revealed a complex mucinous cystadenoma of undetermined malignant potential of the urachus. The cystic spaces were lined by mucin-secreting columnar epithelium that showed focal areas of mild atypia. The epithelium lacked architectural features of villous adenoma. There was no stromal invasion to support an invasive neoplastic process. No pseudomyxoma peritonei was present. The patient was well, with no tumour recurrence, at 6 months follow-up.	bladder
11C-choline PET/CT for restaging of bladder cancer.	AIM: The aim of this study was to evaluate of C-choline PET/CT in bladder cancer (BC) patients with suspected relapse after primary therapy. METHODS: Twenty-five BC patients with surgery (21 [84%]) or radiotherapy (4 [16%]) with curative intent had PET/CT for suspicion of relapse. Mean TNM was T2b N0 M0 (range, T1a N0 M0 to T4 N2 M0), whereas mean age was 71.3 years (range, 50-85 years). Nine (36%) of 25 were treated with adjuvant or salvage chemotherapy within 6 months before PET/CT. Positive findings were validated by histology or correlative imaging and/or clinical follow-up lasting at least 12 months. Age, TNM, histology, previous chemotherapy, and type of primary treatment were correlated with PET/CT positivity by univariate and multivariate binary logistic regression analysis. RESULTS: C-choline PET/CT was positive in 16 (64%) of 25. Six (37.5%) of 16 were positive in residual bladder/bladder bed, with 2 local false positive (FP) and 1 false negative (FN) on lymph nodes (LNs); 3 of 16 patients had PET-positive LNs with 1 FP; 1 of 16 patients showed distant metastases. Two (12.5%) of 16 had positive residual bladder/bladder bed and locoregional LNs; 1 (6.3%) of 16, residual bladder/bladder bed and bone; metastasis, 1 (6.3%) of 16 residual bladder/bladder bed and lung metastasis; 2 (12.5%) of 16, LN and distant metastasis. Five (56%) of 9 of PET negatives were FN in residual bladder/bladder bed. Eighteen (72%) of 25 were validated by histology, with 7 (18%) of 25 by correlative imaging and/or clinical follow-up. C-choline PET/CT was sensitive, specific, and accurate, with good positive and negative predictive values for local relapse of 66.7%, 84.6%, 76%, 80%, and 73.3% and 90%, 93.3%, 92%, 90%, and 93.3% for LNs and distant relapse, respectively. No FP or FN was detected for distant metastasis. None of the investigated factors were statistically significant. CONCLUSION: C-choline PET/CT is useful for restaging BC suspected of relapse, especially for the evaluation of LN or distant metastases.	bladder
Fucoxanthin induces growth arrest and apoptosis in human bladder cancer T24 cells by up-regulation of p21 and down-regulation of mortalin.	Fucoxanthin, a natural carotenoid, has been reported to have anti-cancer activity in human colon cancer cells, human prostate cancer cells, human leukemia cells, and human epithelial cervical cancer cells. This study was undertaken to evaluate the molecular mechanisms of fucoxanthin against human bladder cancer T24 cell line. MTT analysis results showed that 5 and 10 μM fucoxanthin inhibited the proliferation of T24 cells in a dose- and time-dependent manner accompanied by the growth arrest at G0/G1 phase of cell cycle, which is mediated by the up-regulation of p21, a cyclin-dependent kinase (CDK)-inhibitory protein and the down-regulation of CDK-2, CDK-4, cyclin D1, and cyclin E. In addition, 20 and 40 μM fucoxanthin induced apoptosis of T24 cells by the abrogation of mortalin-p53 complex and the reactivation of nuclear mutant-type p53, which also had tumor suppressor function as wild-type p53. All these results demonstrated that the anti-cancer activity of fucoxanthin on T24 cells was associated with cell cycle arrest at G0/G1 phase by up-regulation of p21 at low doses and apoptosis via decrease in the expression level of mortalin, which is a stress regulator and a member of heat shock protein 70, followed by up-regulation of cleaved caspase-3 at high doses.	bladder
Oncological outcomes of advanced muscle-invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum-based chemotherapy.	OBJECTIVE: To assess the oncological outcomes of radical cystectomy (RC) and adjuvant chemotherapy to treat muscle-invasive bladder cancer (MIBC) with a micropapillary component (MPC), and to compare outcomes with those from pure urothelial carcinoma (PUC). MATERIALS AND METHODS: A retrospective review of clinicopathological and follow-up data was performed for all patients treated by RC and adjuvant platinum-based chemotherapy for advanced MIBC in three tertiary reference centers between 1999 and 2012. Uni- and multivariate Cox's regression analyses evaluated the association of the presence of MPC with disease recurrence and cancer-specific mortality. RESULTS: Two hundred and thirty-five (88 %) PUC and 31 (12 %) MPC cases were included. Median age was 65 (39-83) years in the PUC group and 62 (45-80) years in the MPC group. Median survival was 29 months in the MPC versus 31 months in the PUC group. No significant difference was observed between the groups regarding main clinical and pathological characteristics. The median number of treatment cycles administered was 6 (3-8) in the PUC versus 5 (3-8) in the MPC group (p = 0.45). Five-year disease-free recurrence and cancer-specific survival (CSS) rates were 15 and 24 %, respectively, in the MPC versus 42 and 47 %, respectively, in the PUC group (p = 0.007 and 0.058). In multivariate analyses, ASA score, soft tissue surgical margins, and MPC were associated with disease recurrence (p = 0.022, 0.001, and 0.015, respectively). We found no association between MPC and cancer-specific mortality (univariate, p = 0.06). CONCLUSION: MPC was associated with higher recurrence rates after RC and platinum-based adjuvant chemotherapy than that with pure urothelial tumors.	bladder